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Deletion of PI3K-p85alpha gene impairs lineage commitment, terminal maturation, cytokine generation and cytotoxicity of NK cells. Genes Immun 2008 Sep;9(6):522-35

Date

06/13/2008

Pubmed ID

18548087

Pubmed Central ID

PMC4623703

DOI

10.1038/gene.2008.45

Scopus ID

2-s2.0-51249121801   24 Citations

Abstract

Class IA phosphotidylinositol-3-kinases (PI3Ks) are a family of p85/p110 heterodimeric lipid kinases that are important in regulating signaling events in B and T cells. However, their role in natural killer (NK) cells is not understood. Here, using mice that lack the regulatory p85alpha subunit and its alternatively spliced variants p55alpha/p50alpha (collectively termed as p85alpha(-/-)), we defined the role of PI3K in NK cell development and function. p85alpha(-/-) mice had impaired lineage commitment leading to reduced NK cellularity in the bone marrow and liver. p85alpha(-/-) NK cells showed a defective Ly49 subset specification and a decreased expression of CD43. Lack of p85alpha severely reduced the NK-mediated cytotoxicity against tumor cells representing 'induced-self' and 'missing-self'. More importantly, NKG2D and NK1.1 receptor-mediated cytokine and chemokine generation was significantly compromised in p85alpha(-/-) NK cells. These results reveal a previously unrecognized role of p85alpha in the development, terminal maturation, cytokine/chemokine generation and tumor clearance of NK cells.

Author List

Awasthi A, Samarakoon A, Dai X, Wen R, Wang D, Malarkannan S

Authors

Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of Wisconsin
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bone Marrow
Cell Differentiation
Chemokines
Cytokines
Integrin alphaV
Killer Cells, Natural
Leukosialin
Liver
Mice
NK Cell Lectin-Like Receptor Subfamily K
Phosphatidylinositol 3-Kinases
Receptors, Immunologic
Receptors, Natural Killer Cell
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5